Mechanical stretch disrupts intracellular structures under impaired actin integrity in vascular smooth muscle cells

Actin-bundle organization is essential for vascular smooth muscle cell mechanics and is implicated in actin-related diseases. However, it remains unclear how cell stretching affects intracellular actin bundles when actin polymerization is impaired. Here, we performed live imaging of Latrunculin A-treated A7r5 vascular smooth muscle cells in a stretch chamber. GFP– α -actinin imaging showed that Latrunculin A reduced actin-bundle coverage while periodicity was maintained. Subsequent mechanical stretch disrupted both actin-bundle coverage and periodicity. We constructed a stochastic filament bundle model in which actin filament length, actin crosslinking protein dynamics, external stretch, and myosin-driven contractile shortening determine bundle connectivity. The model generated non-spanning, collapse, and persistent states based on spanning connectivity before and after stretch, shaped by filament length and applied strain. A reduced model further showed that these states are governed by a balance between connectivity formation and stretch-induced loss. Together, our results suggest that reduced actin polymerization destabilizes intracellular actin-bundle organization under mechanical stretch, providing a mechanism linking actin polymerization defects to mechanical fragility in vascular smooth muscle cells.